title: Facilitating effects of berberine on rat pancreatic islets through modulating hepatic nuclear factor 4 alpha expression and glucokinase activity.
abstract: OBJECTIVE
  To observe the effect of berberine on insulin secretion in rat pancreatic islets and to explore its possible molecular mechanism.
  
  
  METHODS
  Primary rat islets were isolated from male Sprague-Dawley rats by collagenase digestion and treated with different concentrations (1, 3, 10 and 30 micromol/L) of berberine or 1 micromol/L Glibenclamide (GB) for 24 h. Glucose-stimulated insulin secretion (GSIS) assay was conducted and insulin was determined by radioimmunoassay. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was performed to evaluate cytotoxicity. The mRNA level of hepatic nuclear factor 4 alpha (HNF4alpha) was determined by reverse transcription polymerase chain reaction (RT-PCR). Indirect immunofluorescence staining and Western blot analysis were employed to detect protein expression of HNF4alpha in the islets. Glucokinase (GK) activity was measured by spectrophotometric method.
  
  
  RESULTS
  Berberine enhanced GSIS rather than basal insulin secretion dose-dependently in rat islets and showed no significant cytotoxicity on islet cells at the concentration of 10 mumol/L. Both mRNA and protein expressions of HNF4alpha were up-regulated by berberine in a dose-dependent manner, and GK activity was also increased accordingly. However, GB demonstrated no regulatory effects on HNF4alpha expression or GK activity.
  
  
  CONCLUSIONS
  Berberine can enhance GSIS in rat islets, and probably exerts the insulinotropic effect via a pathway involving HNF4alpha and GK, which is distinct from sulphonylureas (SUs).
authors.affiliation: Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China.
authors.forename: Zhi-Quan
authors.initials: ZQ
authors.lastname: Wang
authors.forename: Fu-Er
authors.initials: FE
authors.lastname: Lu
authors.forename: San-Hua
authors.initials: SH
authors.lastname: Leng
authors.forename: Xin-Sheng
authors.initials: XS
authors.lastname: Fang
authors.forename: Guang
authors.initials: G
authors.lastname: Chen
authors.forename: Zeng-Si
authors.initials: ZS
authors.lastname: Wang
authors.forename: Li-Ping
authors.initials: LP
authors.lastname: Dong
authors.forename: Zhong-Qing
authors.initials: ZQ
authors.lastname: Yan
mesh_terms: D000818:Animals; D001599:Berberine / Q000494:pharmacology*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005941:Glucokinase / Q000378:metabolism*; D005947:Glucose / Q000494:pharmacology; D005905:Glyburide / Q000494:pharmacology; D051557:Hepatocyte Nuclear Factor 4 / Q000378:metabolism*; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010936:Plant Extracts / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D051557:Hepatocyte Nuclear Factor 4; C496594:Hnf4a protein, rat; D007004:Hypoglycemic Agents; D007328:Insulin; D010936:Plant Extracts; D001599:Berberine; D005941:Glucokinase; D005947:Glucose; D005905:Glyburide